Abstract:
The antimalarial drug-resistance conundrum which threatens to reverse the great strides taken to curb the malaria
scourge warrants an urgent need to find novel chemical scaffolds to serve as templates for the development of new
antimalarial drugs. Plants represent a viable alternative source for the discovery of unique potential antiplasmodial
chemical scaffolds. To expedite the discovery of new antiplasmodial compounds from plants, the aim of this
study was to use phylogenetic analysis to identify higher plant orders and families that can be rationally prioritised
for antimalarial drug discovery. We queried the PubMed database for publications documenting antiplasmodial
properties of natural compounds isolated from higher plants. Thereafter, we manually collated compounds reported
along with plant species of origin and relevant pharmacological data. We systematically assigned antiplasmodial-associated
plant species into recognised families and orders, and then computed the resistance index, selectivity index
and physicochemical properties of the compounds from each taxonomic group. Correlating the generated phylogenetic
trees and the biological data of each clade allowed for the identification of 3 ‘hot’ plant orders and families.
The top 3 ranked plant orders were the (i) Caryophyllales, (ii) Buxales, and (iii) Chloranthales. The top 3 ranked plant
families were the (i) Ancistrocladaceae, (ii) Simaroubaceae, and (iii) Buxaceae. The highly active natural compounds
(
IC50 ≤ 1 μM) isolated from these plant orders and families are structurally unique to the ‘legacy’ antimalarial drugs. Our
study was able to identify the most prolific taxa at order and family rank that we propose be prioritised in the search
for potent, safe and drug-like antimalarial molecules.
